Electrocorticographic Changes and Neuronal Maturation in the Antidepressant-like and Anxiolytic Effects of Micro- orMacrodosing of Psilocybe cubensis Mushroom in Mice

Mushroom use dates back to ancient times, and it currently remains significant among indigenous and urban populations as a medicinal option. Psilocybe species are suggested to modify emotions when administered in macro- or microdose form for the treatment of anxiety and depression, both often affected by a delayed onset and adverse effects of current pharmacological therapy. The objective of this study was to evaluate the anxiolytic and/or antidepressant-like effects of P. cubensis mushroom aqueous extract (PcAE) microdosing in mice using open-field and rota-rod tests, followed by plus-maze or forced swimming tests. We also evaluated changes in neuronal activity and dendritic maturation using electrocorticography (ECoG) and immunohistochemical techniques. The outcomes were compared with an effective macrodose of PcAE and antidepressant fluoxetine (FLX). For this study, mice were grouped as follows: (1) vehicle, (2) acute, and (3) repeated (10 days) PcAE microdosing (1 µg/kg); (4) single PcAE macrodose (1 g/kg); and (5) acute and (6) repeated reference drug fluoxetine (FLX, 10 mg/kg).The anxiolytic and antidepressant-like effects using microdosing were similar to those observed with macrodoses of PcAE and FLX; significant dose- and/or time-dependent changes in the ECoG and dendritic maturation of hippocampus neurons were also observed, in addition to altered corticosterone levels. To conclude, P. cubensis mushroom promotes brain effects in mice after micro- and macrodosing, supporting its potential as a therapeutic alternative for mental health.